Recurrent herpetic keratitis is the leading cause of corneal blindness in the U.S. today. The long term goal of the present study is reduce the incidence of visual loss through an improved understanding of the basic mechanisms of HSV-1 latency, reactivation, and recurrent disease. The first proposed specific aim to meet this important long term objective is to study herpes simplex type 1 (HSV-1) gene expression during latency and reactivation. These studies will be carried out in rabbits, mice, and human pathological specimens using (1) cocultivation to demonstrate infectious virus, (2) in situ hybridization with specific gene probes to demonstrate mRNA transcription, and (3) immunohistology with monoclonal antibodies to demonstrate translation of specific proteins. These studies will also test the hypothesis that HSV-1 can establish latency at a peripheral, non- ganglionic ocular site, the cornea, as well as at a central ganglionic site, the trigeminal ganglia. The concept of latency at a peripheral site will also be used to test a new model of herpetic stromal keratitis based on active, limited viral transcription and possible translation within the cornea. The second specific aim is to continue the study of the pharmacology of reactivation of latent HSV-1 in different animal species using the iontophoresis reactivation model. The long term goal is to find a therapeutic agent that will inhibit reactivation of latent HSV-1 in patients with an established history of recurrent disease, and thereby prevent repeated ocular shedding, recurrent disease, and possible blindness in the population at risk.